Management of hereditary hemorrhagic telangiectasia-like symptoms induced by trastuzumab emtansine in a breast cancer patient: case report.

Trastuzumab emtansine (T-DM1) is a targeted therapy combining trastuzumab and emtansine for human epidermal growth factor receptor 2(HER2)-positive breast cancer, with common side effects including fatigue, nausea, pain, headache, low platelet count, and elevated liver enzymes. Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by vascular malformations and telangiectasias in various organs. We present a case of a female patient with advanced breast cancer who developed HHT-like symptoms while on T-DM1 treatment. A 59-year-old woman treated with radiotherapy and T-DM1 every 21 days developed recurring nosebleeds and mucocutaneous and liver telangiectasias indistinguishable from HHT three months after receiving the first dose of T-DM1. Other organ vascular malformations were ruled out through screening protocols. The patient had no previous HHT symptoms or family history. Nasal care measures like lubrication and antifibrinolytics (tranexamic acid) were provided. In addition, propranolol was also prescribed due to its antiangiogenic and antitumoral properties, leading to significantly decreased epistaxis and telangiectasias. Microtubule disruptions caused by T-DM1, along with other angiogenic mechanisms may contribute to the development of telangiectasias resembling HHT. The use of propranolol, an initial approach for HHT, proved to be effective in this case. It is crucial for oncologists and HHT specialists to be aware of this rare adverse event associated with T-DM1 and to implement appropriate management strategies.

Cáncer de mama en el norte del Perú: subtipos moleculares y HER2 low / Breast cancer in northern Peru: molecular subtypes and HER2 low

RESUMEN El objetivo del estudio fue conocer el perfil inmunohistoquímico del cáncer de mama e identificar el subgrupo HER2 low en la macrorregión norte del Perú. Se realizó un estudio transversal con una muestra de 1176 pacientes atendidos en el Instituto Regional de Enfermedades Neoplásicas Norte del Perú desde enero de 2016 a diciembre de 2023. Los datos recolectados (edad, tipo histológico, grado y resultados complementarios), se analizaron con frecuencias y porcentajes. El perfil correspondió a: luminal B (45,6%); luminal A (24,7%); triple negativo (18,2%); y HER2 positivo no luminal (11,5%). Además, HER2 low fueron 215 pacientes (25,1% de los considerados previamente negativos). Este estudio proporciona evidencia que la subtipificación de cáncer de mama ha cambiado, siendo luminal B más frecuente, y es esencial involucrar a políticas de salud para adquirir terapias dirigidas considerando a pacientes HER2 low.

ABSTRACT This study aimed to understand the immunohistochemical profile of breast cancer and to identify the HER2 low subgroup in the northern macro-region of Peru. A cross-sectional study was conducted in 1176 patients from the Regional Institute of Neoplastic Diseases Northern Peru, from January 2016 to December 2023. We analyzed the data (age, histological type, grade and complementary results), with frequencies and percentages. The profile corresponded to: luminal B (45.6%); luminal A (24.7%); triple negative (18.2%); and HER2 positive non luminal (11.5%). In addition, 215 patients presented HER2 low (25.1% of those previously considered negative). This study provides evidence that the subtyping of breast cancer has changed, being luminal B the most frequent. It is essential to involve health policies to acquire targeted therapies considering HER2 low patients.

Análisis de la coexpresión de HER2/GRB7 y su asociación con variables clinicopatológicas en un grupo de mujeres colombianas con diagnóstico de cáncer de mama invasivo / Analysis of HER2/GRB7 co-expression and its association with clinicopathological variables in a group of Colombian women diagnosed with invasive breast cancer

Objetivo. Analizar las diferencias en la presentación de variables clínico-patológicas, de acuerdo con la expresión proteica de GRB7, en tumores HER2 positivos en mujeres colombianas con cáncer de mama invasivo, diagnosticado entre los años 2013 y 2015 en el Instituto Nacional de Cancerología E.S.E (INC). Métodos. Se incluyeron 158 pacientes con diagnóstico confirmado de cáncer de mama ductal invasivo. Se evaluó la expresión de los receptores hormonales (receptor de estrógeno (RE) y de progesterona (RP)), HER2, Ki67 y GRB7, mediante inmunohistoquímica (IHQ), y a partir de estos, se clasificaron los tumores en subtipos intrínsecos. Los análisis estadísticos incluyeron las pruebas de Chi-cuadrado/test exacto de Fisher para las variables categóricas, y la prueba U Mann Whitney/ Kruskal Wallis para las variables cuantitativas. Se evaluó la supervivencia global (SG) y libre de enfermedad (SLR) según la coexpresión de HER2/GRB7 usando el método de Kaplan-Meier y el test de log-rank. Resultados. La expresión de GRB7 se observó exclusivamente en tumores HER2-positivos (luminal B/HER2+ y HER2-enriquecidos: p<0,001). Los casos HER2+/GRB7+ mostraron una mayor expresión de Ki67 (40% vs. 27,5%, p=0,029), pero una tendencia a presentar un menor tamaño tumoral (30 mm vs. 51 mm, p=0,097), comparado con los tumores HER2+/GRB7-. No obstante, no se observaron diferencias en la supervivencia según la coexpresión de HER2/GRB7 (SG: p=0,6; SLR: p=0,07). Conclusiones. En nuestra muestra de estudio, la expresión de GRB7 en tumores HER2+ no se asoció con características clínico-patológicas de pronóstico desfavorable.

Objective: To analyze differences in the presentation of clinicopathological variables according to GRB7 protein expression in HER2-positive tumors in Colombian patients with invasive ductal breast carcinomas diagnosed between 2013 and 2015 at the Instituto Nacional de Cancerología (Bogotá, Colombia).Methods: A total of 158 breast cancer patients were included with a confirmed diagnosis of invasive ductal carcinoma. A single pathologist evaluated the protein expression of hormone receptors (estrogen (ER) and progesterone receptor (PR)), HER2, Ki67, and GRB7 by immunohistochemistry (IHC). The chi-square and Fisher's exact tests were used to assess differences between categorical variables, as well as the Mann-Whitney/Kruskal-Wallis U test for numerical variables. Overall (OS) and disease-free (DFS) survival were evaluated according to HER2/GRB7 co-expression using the Kaplan-Meier method and log-rank test.Results:GRB7 expression was observed exclusively in HER2-positive tumors (luminal B/HER2+ and HER2-enriched: p<0.001). HER2+/GRB7+ cases showed higher Ki67 expression (40% vs. 27.5%, p=0.029) and a tendency to present a smaller tumor (30 mm vs. 51 mm, p=0.097) compared to HER2+/GRB7- tumors. However, no differences in OS or DFS were observed by HER2/GRB7 co-expression (OS: p=0.6; DFS: p=0.07).Conclusions:Our results in Colombian patients indicate that GRB7 expression in HER2-positive breast tumors is not associated with unfavorable clinicopathological features.

Tratamiento sistémico para el cáncer de mama HER2 positivo avanzado. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Systemic treatment for advanced HER2 positive breast cancer. Review of the evidence and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

El cáncer de mama es la neoplasia más frecuente y de mayor mortalidad en las mujeres en todo el mundo. El receptor 2 del factor de crecimiento epidérmico humano (HER2) se sobreexpresa en aproximadamente el 20% de las pacientes con cáncer de mama y se asocia a mayor riesgo de recidiva tumoral y mortalidad. Antes del desarrollo de los anticuerpos monoclonales dirigidos contra HER2, el cáncer de mama HER2 positivo estaba asociado con un pronóstico desfavorable. El uso de las terapias dirigidas anti HER2 ha mejorado significativamente las tasas de supervivencia global tanto en el escenario adyuvante como en la enfermedad metastásica. En los últimos años han surgido nuevos medicamentos que bloquean esta vía de señalización, lo cual ha permitido establecer varias líneas de tratamiento con terapia anti HER2 en las pacientes con enfermedad metastásica. Por esta razón, las unidades funcionales de Oncología Clínica/Seno y Tejidos Blandos tomaron la decisión de realizar una revisión de la evidencia científica disponible a octubre de 2021, para establecer las recomendaciones en el abordaje terapéutico de las pacientes con cáncer de mama metastásico HER2 positivo en el Instituto Nacional de Cancerología (INC).

Breast cancer is the most common neoplasm and the one with the highest mortality in women worldwide. Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% of breast cancer patients and is associated with an increased risk of tumor recurrence and mortality. Before the development of monoclonal antibodies directed against HER2, HER2-positive breast cancer was associated with a poor prognosis. The use of anti-HER2 targeted therapies has significantly improved overall survival rates both in the adjuvant setting and in metastatic disease. In recent years, new drugs have emerged that block this signaling pathway, which has made it possible to establish several lines of treatment with anti-HER2 therapy in patients with metastatic disease. For this reason, the clinical oncology/breast and soft tissue functional units made the decision to conduct a review of the available scientific evidence as of October 2021 to establish recommendations for the therapeutic approach to patients with HER2-positive metastatic breast cancer in the National Cancer Institute (INC).

Indicaciones para el uso de pertuzumab en cáncer de mama HER2 positivono metastásico en los escenarios neoadyuvante y adyuvante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Indications for the use of pertuzumab in non-metastatic HER2-positive breast cancer in the neoadjuvant and adjuvant. Review of the literature and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La adición de la terapia dirigida a la quimioterapia citotóxica en pacientes con cáncer de mama ha mejorado significativamente los desenlaces oncológicos en las pacientes con tumores HER2 positivo. El uso de pertuzumab durante el manejo neoadyuvante incrementa significativamente la respuesta patológica completa y en la actualidad permite emplear regímenes libres de antraciclinas con una eficacia similar y menores efectos cardiovasculares (en especial sobre la fracción de eyección). El beneficio en supervivencia libre de enfermedad invasiva, de adicionar pertuzumab en el escenario adyuvante en las pacientes sin tratamiento anti HER2 previo, está limitado a aquellas con ganglios positivos. La implementación de esquemas con bloqueo dual anti HER2, durante el tratamiento inicial del cáncer de mama HER2 positivo, mejora significativamente el pronóstico oncológico en este grupo de pacientes.

The addition of targeted therapy to cytotoxic chemotherapy in patients with breast cancer has significantly improved oncologic outcomes in patients with HER2-positive tumors. The use of pertuzumab during neoadjuvant management significantly increases the complete pathological response and currently allows the use of anthracycline-free regimens with similar efficacy and fewer cardiovascular effects (especially on ejection fraction). The benefit of pertuzumab in disease-free survival in the adjuvant setting for patients without prior anti-HER2 treatment is limited to those with positive nodes. The implementation of schemes with dual anti-HER2 blockade during the initial treatment of HER2-positive breast cancer significantly improves the oncological outcomes in this group of patients.

Association of genetic ancestry with HER2, GRB7 AND estrogen receptor expression among Colombian women with breast cancer.

Background: Our previous study reported higher mRNA levels of the human epidermal growth factor receptor 2 (HER2)-amplicon genes ERBB2 and GRB7 in estrogen receptor (ER)-positive breast cancer patients with relatively high Indigenous American (IA) ancestry from Colombia. Even though the protein expression of HER2 and GRB7 is highly correlated, they may also express independently, an event that could change the patients' prognosis. In this study, we aimed to explore the differences in ER, HER2 and GRB7 protein expression according to genetic ancestry, to further assess the clinical implications of this association. Methods: We estimated genetic ancestry from non-tumoral breast tissue DNA and assessed tumoral protein expression of ER, HER2, and GRB7 by immunohistochemistry in a cohort of Colombian patients from different health institutions. We used binomial and multinomial logistic regression models to test the association between genetic ancestry and protein expression. Kaplan-Meier and log-rank tests were used to evaluate the effect of HER2/GRB7 co-expression on patients' survival. Results: Our results show that patients with higher IA ancestry have higher odds of having HER2+/GRB7- breast tumors, compared to the HER2-/GRB7- subtype, and this association seems to be stronger among ER-positive tumors (ER+/HER2+/GRB7-: OR=3.04, 95% CI, 1.47-6.37, p<0.05). However, in the multivariate model this association was attenuated (OR=1.80, 95% CI, 0.72-4.44, p=0.19). On the other hand, it was observed that having a higher European ancestry patients presented lower odds of ER+/HER2+/GRB7- breast tumors, this association remained significant in the multivariate model (OR=0.36, 95% CI, 0.13 - 0.93, p= 0.0395). The survival analysis according to HER2/GRB7 co-expression did not show statistically significant differences in the overall survival and recurrence-free survival. Conclusions: Our results suggest that Colombian patients with higher IA ancestry and a lower European fraction have higher odds of ER+/HER2+/GRB7- tumors compared to ER+/HER2-/GRB7- disease. However, this association does not seem to be associated with patients' overall or recurrence-free survival.

Tratamiento Neoadyuvante en cáncer de mama HER2 positivo. La era de la terapia dirigida / Neoadjuvant treatment in HER2 positive breast cancer. The Age of Targeted Therapy

Introducción: El tratamiento neodyuvante del cáncer de mama HER2 positivo ha ido evolucionando a través del tiempo, con la implementación de nuevas estrategias de manejo terapéutico. Es de esta manera como el trastuzumab, un anticuerpo monoclonal anti-HER2sigue siendo el tratamiento estándar en este subtipo de cáncer, los primeros estudios en los que se evidencia su eficacia son el realizado por el Dr. Buzdar y el estudio NOAH en los cuales las pacientes alcanzaron mayores tasas de respuesta patológica completa en comparación con quimioterapia sola, así como también un mayor número de cirugías conservadoras de mama en lugar de mastectomía.Con el paso de los años se han ido desarrollando nuevas estrategias de manejo terapéutico, así tenemos el doble bloqueo anti-HER2 con los anticuerpos monoclonales trastuzumab y pertuzumab que han mejorado las tasas de respuesta patológica completa. Además se ha incluido al lapatinib un inhibidor de tirosina quinasa como parte de las terapias dirigidas. Se ha dilucidado si las antraciclinas confieren un beneficio adicional al tratamiento neoadyuvante y los estudios demuestran que el beneficio es el mismo queotros esquemas de quimioterapia. Es en realidad la quimioterapia indispensable en la neoadyuvancia, el estudio PHERGain demuestra que existen pacientes que pueden alcanzar respuesta patológica completa solo con el doble bloqueo anti-her2 (trastuzumab y pertuzumab) lo que evitaría la toxicidad innecesaria por quimioterapia, y se podrían desarrollar estrategias para el manejo de aquellas pacientes que no alcanzaron una respuestapatológica completa posterior al doble bloqueo. Aún queda un campo amplio por explorar y con estudios en curso al momento. Palabras claves:DsCS:Receptor ErbB-2, Trastuzumab, Neoplasias de la Mama, Quimioterapia Adyuvante, Ado-Trastuzumab Emtansina

Introduction:The neodyuvanttreatment of HER2 positive breast cancer has evolved over time, with the implementation of new therapeutic management strategies. It is in this way that trastuzumab, an anti-HER2 monoclonal antibody continues to be the standard treatment in this subtype of cancer, the first studies in which its efficacy is evidenced are the one carried out by Dr. Buzdar and the NOAH study in which patients achieved higher rates of complete pathological response compared to chemotherapy alone, as well as a higher number of breast-conserving surgeries rather than mastectomy.Over the years, new therapeutic management strategies have been developed, thus we have the double anti-HER2 blockade with the monoclonal antibodies trastuzumab and pertuzumab that have improved the ratesof complete pathological response. In addition, lapatinib, a tyrosine kinase inhibitor, has been included as part of targeted therapies. It has been elucidated whether anthracyclines confer an additional benefit to neoadjuvant treatment and studies show that the benefit is the same as other chemotherapy regimens.It is actually the essential chemotherapy in neoadjuvant therapy, the PHERGain study shows that there are patients who can achieve a complete pathological response only with the double anti-her2 blockade (trastuzumab and pertuzumab), which would avoid unnecessary toxicity due to chemotherapy, and strategies could be developed for the management of those patients who did not achieve a complete pathological response after double blockade. There is still a wide field to explore and with studies underway at the moment. Keywords:MESH:Receptor, ErbB-2;Trastuzumab; Breast Neoplasms; Chemotherapy, Adjuvant; Ado-Trastuzumab Emtansine

Diagnóstico y tratamiento del cáncer de mama HER2+: Guía de Práctica Clínica de la Sociedad Peruana de Cancerología / Diagnosis and treatment of HER2 + breast cancer: Clinical Practice Guide of the Peruvian Society of Cancerology

RESUMEN Introducción. En Perú, el cáncer de mama representa el tipo de cáncer más frecuente en mujeres y el sexto tipo de cáncer más letal en la población general. La sobreexpresión del receptor del factor de crecimiento epidérmico (HER2+) ocurre en 20% a 30% de los cánceres de mama, y se asocia con tumores más agresivos, con mayor recurrencia y mayor mortalidad. Objetivo. Elaborar un conjunto de recomendaciones basadas en evidencias para el diagnóstico y tratamiento del cáncer de mama HER2+, con la finalidad de contribuir a reducir la mortalidad, progresión de la enfermedad y mejorar la calidad de vida. Métodos. Se conformó un panel de especialistas clínicos y metodólogos, quienes identificaron preguntas clínicas relevantes sobre el diagnóstico y tratamiento del cáncer de mama HER2+. Se desarrolló una búsqueda sistemática de GPC en Medline (PubMed), y en organismos elaboradores y recopiladores. Para la formulación de recomendaciones, el panel de especialistas discutió la evidencia y elementos del contexto de implementación de la recomendación, siguiendo la metodología propuesta por el Ministerio de Salud del Perú. Resultados. Se priorizó nueve preguntas clínicas. Se formuló un total de 25 recomendaciones clínicas. Conclusiones. Se elaboró una GPC basada en evidencias, a través de un proceso sistemático, riguroso y transparente desarrollado por un equipo multidisciplinario.

ABSTRACT Introduction. In Peru, breast cancer represents the most common type of cancer in women and the sixth most lethal type of cancer in the general population. Overexpression of the epidermal growth factor receptor (HER2 +) occurs in 20% to 30% of breast cancers, and is associated with more aggressive tumors, with greater recurrence and greater mortality. Objective. Prepare a set of evidence-based recommendations for the diagnosis and treatment of HER2 + breast cancer, in order to help reduce mortality, disease progression and improve quality of life. Methods. A panel of clinical specialists and methodologists was formed, who identified relevant clinical questions about the diagnosis and treatment of HER2 + breast cancer. A systematic search for CPGs was carried out in Medline (PubMed), and in developing and compiling agencies. For the formulation of recommendations, the panel of specialists discussed the evidence and elements of the context of implementation of the recommendation, following the methodology proposed by the Ministry of Health of Peru. Results. Nine clinical questions were prioritized. A total of 25 clinical recommendations were made. Conclusions. An evidence-based CPG was developed through a systematic, rigorous and transparent process developed by a multidisciplinary team.

Tratamiento del Cáncer de Mama Metastásico, Receptor Hormonal Positivo, Her 2 Negativo: Enfoque actual a Dianas Terapéuticas / Treatment of Metastatic Breast Cancer, Hormone Receptor Positive, Her 2 Negative: Current Approach to Therapeutic Targets

En el cáncer de mama luminal, la terapia hormonal está indicada en adyuvancia y neoadyuvancia. El estadio metastásico incluye un grupo heterogéneo de tumores que varían de acuerdo con el sitio de metástasis, tiempo de aparición, condición general de las pacientes, entre otras características intrínsecas del tumor. Esto establece tiempos de sobrevida con rangos variables de meses a muchos años. Los estrógenos actúan en receptores de membrana citoplasmática y nuclear: en las células neoplásicas estimulan la transcripción del ARN, con persistencia de la proliferación. El bloqueo de la acción hormonal en el cáncer avanzado encuentra mecanismos de resistencia con el uso de vías de señalización paralelas, este conocimiento ha permitido el desarrollo de inhibidores de CDK 4/6, mTOR y PIK3-CA, que se recomiendan en enfermedad metastásica, con prolongación significativa de la supervivencia global. En crisis visceral aún se mantiene el uso de quimioterapia sistémica secuencial o combinada

For a patient with estrogen receptor positivebreast cancer, the adjuvant and neoadjuvant endocrine therapy has an absolute benefit. The metastatic stage includes a diverse group of tumors that vary according to the site of metastasis, time of appear, general condition of the patients, and other intrinsic characteristics of the tumor. survival in cancer varies according these features, from a few months to many years. Estrogen hormones stimulate nuclear and cytoplasmic receptors. In neoplastic cells, estrogen regulate RNA transcription, with persistence of proliferation. The blocking of hormonal action in metastatic cancer, has resistance mechanisms with the use of parallel signaling pathways, this knowledge has allowed the development of inhibitors of CDK 4/6, mTOR and PIK3-CA, which are recommended in metastatic disease. with significant prolongation of overall survival. In visceral crisis, the use of sequential or combined systemic chemotherapy is still maintained

Accuracy of breast magnetic resonance imaging in evaluating the response to neoadjuvant chemotherapy: a study of 310 cases at a cancer center.

OBJECTIVE: To evaluate the accuracy of magnetic resonance imaging (MRI) of the breasts in the identification of a pathological complete response in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This was a single-center, retrospective, observational study designed to validate a diagnostic test. The following variables were evaluated: age; results of the histological and immunohistochemical analysis of the biopsy; post-NAC MRI findings; and results of the histological analysis of the surgical specimen, using the residual cancer burden index. The radiological response, as assessed by MRI, was compared with the pathological response, as assessed by histological analysis of the surgical specimen (the gold standard method). RESULTS: We evaluated 310 tumors in 308 patients. The mean age of the patients was 47 years (range, 27-85 years). For identifying a pathological complete response, breast MRI had an overall accuracy of 79%, with a sensitivity of 75%, specificity of 83%, positive predictive value of 75%, and negative predictive value of 83%. When that accuracy was stratified by molecular subtype, it was best for the HER2 subtype, with a sensitivity and specificity of 82% and 89%, respectively, followed by the triple-negative subtype, with a sensitivity and specificity of 78% and 83%, respectively. CONCLUSION: Breast MRI showed good accuracy in the prediction of a pathological complete response after NAC. The sensitivity and positive predictive value were highest for the HER2 and triple-negative subtypes.

OBJETIVO: Avaliar a acurácia da ressonância magnética (RM) das mamas na identificação de resposta patológica completa em pacientes com câncer de mama submetidas a quimioterapia neoadjuvante (QTN). MATERIAIS E MÉTODOS: Teste de validação diagnóstica, realizado por meio de estudo observacional, unicêntrico e retrospectivo. As variáveis avaliadas no estudo foram idade, resultado histológico e imuno-histoquímico da biópsia, análise da RM após QTN e análise histológica da peça cirúrgica, com cálculo do índice residual cancer burden. Os resultados da resposta radiológica pela RM foram comparados com a resposta patológica na peça cirúrgica (padrão ouro). RESULTADOS: Foram incluídos 310 tumores de 308 pacientes com média de idade de 47 anos (variação: 27 a 85 anos). A acurácia da RM foi 79%, com sensibilidade de 75%, especificidade de 83%, valor preditivo positivo de 75% e valor preditivo negativo de 83%. Estratificando-se por subtipo molecular, a detecção da resposta patológica pela RM obteve os melhores porcentuais de acerto no subtipo HER2 superexpresso, com sensibilidade e especificidade de 82% e 89%, respectivamente, seguido do subtipo triplo negativo, com sensibilidade e especificidade de 78% e 83%, respectivamente. CONCLUSÃO: A RM demonstrou boa acurácia na predição de resposta patológica completa após QTN. A sensibilidade e o valor preditivo positivo foram mais altos nos subtipos triplo negativo e HER2 superexpresso.

Accuracy of breast magnetic resonance imaging in evaluating the response to neoadjuvant chemotherapy: a study of 310 cases at a cancer center / Acurácia da ressonância magnética das mamas na avaliação da resposta a quimioterapia neoadjuvante: estudo de 310 casos em um centro oncológico

Abstract Objective: To evaluate the accuracy of magnetic resonance imaging (MRI) of the breasts in the identification of a pathological complete response in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: This was a single-center, retrospective, observational study designed to validate a diagnostic test. The following variables were evaluated: age; results of the histological and immunohistochemical analysis of the biopsy; post-NAC MRI findings; and results of the histological analysis of the surgical specimen, using the residual cancer burden index. The radiological response, as assessed by MRI, was compared with the pathological response, as assessed by histological analysis of the surgical specimen (the gold standard method). Results: We evaluated 310 tumors in 308 patients. The mean age of the patients was 47 years (range, 27-85 years). For identifying a pathological complete response, breast MRI had an overall accuracy of 79%, with a sensitivity of 75%, specificity of 83%, positive predictive value of 75%, and negative predictive value of 83%. When that accuracy was stratified by molecular subtype, it was best for the HER2 subtype, with a sensitivity and specificity of 82% and 89%, respectively, followed by the triple-negative subtype, with a sensitivity and specificity of 78% and 83%, respectively. Conclusion: Breast MRI showed good accuracy in the prediction of a pathological complete response after NAC. The sensitivity and positive predictive value were highest for the HER2 and triple-negative subtypes.

Resumo Objetivo: Avaliar a acurácia da ressonância magnética (RM) das mamas na identificação de resposta patológica completa em pacientes com câncer de mama submetidas a quimioterapia neoadjuvante (QTN). Materiais e Métodos: Teste de validação diagnóstica, realizado por meio de estudo observacional, unicêntrico e retrospectivo. As variáveis avaliadas no estudo foram idade, resultado histológico e imuno-histoquímico da biópsia, análise da RM após QTN e análise histológica da peça cirúrgica, com cálculo do índice residual cancer burden. Os resultados da resposta radiológica pela RM foram comparados com a resposta patológica na peça cirúrgica (padrão ouro). Resultados: Foram incluídos 310 tumores de 308 pacientes com média de idade de 47 anos (variação: 27 a 85 anos). A acurácia da RM foi 79%, com sensibilidade de 75%, especificidade de 83%, valor preditivo positivo de 75% e valor preditivo negativo de 83%. Estratificando-se por subtipo molecular, a detecção da resposta patológica pela RM obteve os melhores porcentuais de acerto no subtipo HER2 superexpresso, com sensibilidade e especificidade de 82% e 89%, respectivamente, seguido do subtipo triplo negativo, com sensibilidade e especificidade de 78% e 83%, respectivamente. Conclusão: A RM demonstrou boa acurácia na predição de resposta patológica completa após QTN. A sensibilidade e o valor preditivo positivo foram mais altos nos subtipos triplo negativo e HER2 superexpresso.

Parámetros de la 18F-FDG PET/CT asociado con los factores pronósticos en la estadificación inicial del Cáncer de Mama / Parameters of the 18F-FDG PET/CT associated with the prognostic factors in the initial staging of Breast Cancer

Propósito de la revisión: Este artículo tiene la siguiente pregunta de investigación: ¿Se debe considerar la Biología, histología y el fenotipo para la estadificación inicial del Cáncer de Mama? Se realiza una revisión del estudio metabólico del cáncer de mama (CM) con la técnica de la captación de glucosa Fluorada 18-Fluoro-2-Desoxi-D-Glucosa y su medición de intensidad con tomografía por Emisión de positrones (18F-FDG PET/CT). Recientes Hallazgos: La 18F-FDG PET/CT puede detectar metástasis que no son visibles en otras modalidades, el carcinoma ductal invasivo muestra una mayor captación que el carcinoma lobular invasivo. La alta captación de 18F-FDG se ha asociado con un resultado peor y una supervivencia más corta. Extracto: El cáncer de mama es un tipo heterogéneo de malignidad porque varios factores afectan su comportamiento y pronóstico. Debido a esta heterogeneidad, el tratamiento óptimo y la respuesta esperada al tratamiento puede variar sustancialmente para cada paciente. 18F-FDG PET/CT puede proporcionar información relevante sobre el metabolismo, el diagnóstico y el pronóstico del cáncer de mama. Varios estudios han sugerido una correlación entre las características clínico-patológicas del cáncer de mama y los parámetros metabólicos obtenidos por 18F-FDG PET/CT.

Purpose of the review: This article has the following research question: Should biology, histology and phenotype be considered for initial staging of breast cancer? A review of the metabolic study of breast cancer (CM) is performed with the technique of glucose uptake Fluorada 18-Fluoro-2-Deoxy-D-Glucose and its intensity measurement with positron emission tomography (18F-FDG PET / CT). Recent Findings: 18F-FDG PET / CT can detect metastases that are not visible in other modalities, invasive ductal carcinoma shows a higher uptake than invasive lobular carcinoma. The high uptake of 18F-FDG has been associated with a worse outcome and shorter survival. Excerpt: Breast cancer is a heterogeneous type of malignancy because several factors affect its behavior and prognosis. Due to this heterogeneity, the optimal treatment and the expected response to treatment may vary substantially for each patient. 18F-FDG PET / CT can provide relevant information on the metabolism, diagnosis and prognosis of breast cancer. Several studies have suggested a correlation between the clinical-pathological characteristics of breast cancer and the metabolic parameters obtained by 18F-FDG PET / CT.

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma / Receptores HER2, compromiso ganglionar axilar y sobrevida en mujeres con cáncer de mama ductal invasivo

ABSTRACT Background: Breast cancer (BC) is the most common malignancy in women. Aim: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. Patients and Methods: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. Results: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. Conclusions: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.

Antecedentes: El cáncer de mama es el tumor maligno más común en mujeres. Objetivo: Conocer el impacto del estado HER2 sobre el compromiso ganglionar axilar al momento del diagnóstico y durante los primeros cuatro años después de la cirugía en mujeres con carcinoma ductal invasivo de tipo no especial (IDC-NST). Pacientes y Métodos: Incluimos retrospectivamente a 375 mujeres en etapas clínicas iniciales de IDC-NST que fueron operadas en un hospital clínico. Ellas se dividieron en grupos de acuerdo al fenotipo: HR+HER2-, HR+HER2+, HR-HER2+y HR-HER2-. La disección de ganglios axilares se efectuó solo en las pacientes con macrometástasis en el ganglio centinela. Si había más de tres ganglios comprometidos, se efectuó radioterapia. Todas las pacientes se trataron con quimioterapia. Las pacientes HER2+ recibieron trastuzumab y las pacientes HR+ recibieron hormonoterapia. Resultados: Tumores más grandes, de mayor grado de malignidad, HR+, HER2+ y la invasión linfovascular fueron predictivos de la presencia de metástasis axilares al momento del diagnóstico. La sobrevida más baja se observó en pacientes HR-HER2+. La sobrevida libre de recurrencia locorregional más baja, se observó en pacientes HR-HER2+ y HR-HER2-. HER2 no fue predictor de sobrevida. Conclusiones: En estas mujeres, HER2+fue predictor de la presencia de compromiso ganglionar axilar al momento del diagnóstico pero no de la sobrevida a cuatro años.

Características y supervivencia de pacientes con cáncer de seno metastásico HER2-positivo en la era post-trastuzumab / Characteristics and survival of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era

Resumen Introducción: Existen múltiples factores pronóstico de la supervivencia en el cáncer de mama metastásico (CMM). Los dos factores mejor estudiados son la expresión de receptores hormonales (RH) y el estatus HER2, por lo que su determinación es obligada en toda paciente con diagnóstico de CMM. El 80% de los tumores expresan RH y el 20% son HER2-positivo. El objetivo de este estudio es determinar los factores pronóstico de la supervivencia global (SG) de pacientes con diagnóstico de CMM HER2-positivo atendidos entre 2009 y 2015 en el Instituto de Cancerología de Medellín (Colombia). Métodos: Estudio observacional retrospectivo. Se realizaron las curvas de supervivencia mediante el método de Kaplan-Meier comparadas con Log-Rank test y se analizaron los factores que influyeron en la supervivencia mediante la regresión de Cox. Resultados: Se incluyeron 101 pacientes. La mediana de seguimiento fue 46,6 meses (rango 13-155 meses), la SG a cinco años fue 41% (IC95%: 31%-50%) y a diez años 13% (IC95%: 4%-30%). Tuvieron mayor SG pacientes con enfermedad en recaída, con estadios I y II, las mayores de 40 años, menopáusicas, con tumores con grado histológico bajo y co-expresión de receptores hormonales. Las pacientes que recayeron tuvieron mayor SG que las que hicieron metástasis de novo (HR: 0,47, IC95%: 0,27-0,81) ajustado por las otras variables. Conclusiones: La supervivencia de estas pacientes fue semejante al de otros países, al igual que las líneas de tratamiento y la terapia recibida.

Abstract Introduction: There are multiple risk factors associated with the prognosis of survival of metastatic breast cancer (MBC). The two major risk factors are the expression of hormonal receptors (HR) and HER 2 neu, and the reason why they are requested in every MBC patient. The large majority (80%) of breast tumors are HR positive, and 20% are HER 2 positive. The aim of this study was to determine the prognostic factors associated with the overall survival (OS) of patients diagnosed with HER 2 positive MBC seen between January 2009 and December 2015 in the Instituto de Cancerología (Medellín-Colombia). Methods: A retrospective observational study was conducted, with survival analysis using the Kaplan-Meier method. The survival curves were compared using the Log-Rank Test, and factors associated with survival were analyzed using the Cox regression. Results: 101 patients were included in the study. The median survival time was 46.6 months (Range 13-155 months), the 5-year OS was 41% (95% CI; 31%-50%) and the 10-year OS 13% (95% CI; 4%-30%). Higher overall survival was found for patients with relapsed disease, those with stages I and II, patients older than 40 years, postmenopausal, tumors with low histological grade and with co-expression of hormonal receptors. The patients with relapse of disease had a higher OS than the de novo patients after being adjusted for the other factors (HR: 0.47, 95% CI; 0.27-0.1). Discussion: The overall survival time is similar to that of other countries, as well as the lines of treatment and therapy received.

Mucina 4 en cáncer de mama HER2 positivo, en pacientes del Hospital Oncológico Provincial de Córdoba / Mucin 4 in HER2-positive breast cancer, in patients from the Hospital Oncológico Provincial de Córdoba

OBJETIVOS Determinar prevalencia de sobreexpresión de MUC-4 en pacientes con cáncer de mama HER 2 positivo homogéneamente tratadas en el Hospital Oncológico durante el período 2014­2017 que hayan recibido cualquier esquema terapéutico con trastuzumab. Como objetivo secundario analizar la supervivencia libre de progresión (SLP) en pacientes con positividad de sobreexpresión de MUC4. MATERIALES Y MÉTODOS Estudio observacional, retrospectivo y descriptivo de corte transversal realizado en Hospital Oncológico Provincial de Córdoba en pacientes con diagnóstico de cáncer de mama HER-2 positivo que hayan recibido tratamiento con trastuzumab durante el período 01/01/2014-31/12/2017 y análisis de SLP en relación con los factores pronósticos y predictivos en cáncer de mama e identificación de potencial biomarcador predictivo. Mediana de seguimiento 36 meses. RESULTADOS La tasa de prevalencia muestral de sobreexpresión de MUC-4, sobre el total de muestras que pudieron ser analizadas fue del 0.66. El análisis incluyó 62 pacientes mujeres que realizaron tratamiento anti - HER 2 con cualquier esquema, que contenga Trastuzumab la SLP global a los 36 meses fue de 79,8% (IC 95% 66,27 ­ 88,43). El compromiso ganglionar se asoció con una tendencia negativa a la SLP, aunque sin diferencia estadísticamente significativa p=0,07. La SLP a 18 meses en 12 pacientes con MUC-4 positivo fue de 63,6% (IC 95% 29,6 ­ 84,5). DISCUSIÓN La tasa de SLP a 3 años en 62 pacientes con cáncer de mama HER 2 positivo tratadas en Hospital Oncológico, durante el periodo 2014-2017 fue de 79,8% (IC 95% 66,27­88,43), valor aceptable teniendo en cuenta las referencias de los estudios pivotales. Los factores pronósticos y predictivos actualmente validados en cáncer de mama parecen influir con tendencia hacia la disminución de la SLP, principalmente la presencia de compromiso ganglionar. La presencia de positividad para la marcación de la glicoproteína MUC-4, según datos precoces, parece influir en forma negativa sobre la SLP

Her2 expression as a prognostic factor in metastatic gastric cancer

ABSTRACT Background - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population. Objective - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes. Methods - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value <0.05 was considered statistically significant. Results - Forty-nine patients were included in this study. However, only 32 had samples assessed for HER2 expression. Five (16%) patients were positive. Among HER2-negative patients, the average age was 54 years, 44% received a treatment protocol with three drugs, 70% had a performance status score 0-1, and 41% had well or moderately differentiated histology. Among HER2-positive patients, the average age was 58 years, 40% received three drugs, 100% had a performance status score 0-1, and 67% had well or moderately differentiated histology. Response rate was evaluated in 28 cases, and there was no difference between the groups (HER2-negative 52% vs. HER2-positive 40%; P=0.62). Survival outcomes were numerically worse among HER2-positive patients. Median progression-free survival was 8.3 months for HER2-positive patients and 10.6 months for HER2-negative patients (HR 1.61, 95% CI: 0.59-4.38); median overall survival was 14.8 months and 16.9 months for HER2-positive and HER2-negative patients, respectively (HR 1.52, 95% CI: 0.50-4.66). Conclusion - HER2 overexpression in metastatic gastric cancer patients may be a predictor of poor prognosis and further validation is warranted.

RESUMO Contexto - O receptor 2 do fator de crescimento epidermal humano (EGFR2/HER2/ErbB2) é um receptor transmembrana que estimula a proliferação celular quando ativado. A expressão de HER2 foi estudada em diversas neoplasias, como câncer gástrico. No entanto, sua relação com a sobrevida dos pacientes com câncer gástrico metastático permanece desconhecida. Além disso, há falta de informação sobre este assunto na população brasileira. Objetivo - Avaliar a proporção de pacientes cujas células tumorais expressam HER2 e correlacionar essa característica com aspectos clínicos e também com os desfechos do tratamento. Métodos - Este é um estudo retrospectivo. Foram incluídos pacientes adultos com câncer gástrico metastático tratados em um Hospital Geral Universitário entre 2011 e 2015. Nenhum paciente recebeu terapia anti-HER2. A expressão do receptor foi avaliada por imuno-histoquímica. Fatores de risco para a sobrevida foram avaliados com regressão de Cox univariada e valor P<0,05 foi considerado estatisticamente significativo. Resultados - Quarenta e nove pacientes foram incluídos neste estudo. No entanto, 32 tiveram amostras avaliadas para expressão de HER2. Cinco (16%) pacientes foram positivos. Entre os pacientes HER2 negativos: a idade média foi de 54 anos, 44% receberam um protocolo com três drogas, 70% apresentavam um score de status performance 0-1, 41% tinham histologia bem ou moderada diferenciada. Entre os pacientes HER2 positivos: a média de idade foi de 58 anos, 40% receberam três drogas, 100% apresentavam um score de status performance de 0-1, 67% tinham histologia bem ou moderada diferenciada. A taxa de resposta foi avaliada em 28 casos e não houve diferença entre os grupos (HER2 negativo 52% e HER2 positivo de 40%; P=0,62). A sobrevida foi menor entre pacientes HER2 positivos. As medianas de Sobrevida Livre de Progressão foram 8,3 meses e 10,6 meses, respectivamente (HR 1,61; IC 95%: 0,59-4,38). As medianas de Sobrevida Global foram 14,8 meses e 16,9 meses, respectivamente (HR 1,52; IC 95%: 0,50-4,66). Conclusão - A expressão tumoral de HER2 pode ser um fator de pior prognóstico para pacientes portadores de câncer gástrico metastático e uma validação futura desses achados se faz necessária.

Outcomes of Hispanic women with lymph-node positive, HER2 positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab in Mexico.

INTRODUCTION: Evidence regarding the outcomes of Hispanic women with breast cancer is lacking. We analyzed women with HER2+ disease treated with trastuzumab-based neoadjuvant chemotherapy in Mexico. METHODS: 244 patients were included. Outcomes were compared between patients who achieved pathologic complete response (pCR) (n = 119), or less than pCR (n = 125). Patients with noninvasive (ypT0/is, ypN0) residual disease were also analyzed. RESULTS: 119 (48.8%) patients achieved pCR. pCR was the only factor associated with improved 3 year survival (98.1% vs 92.3%: P = 0.02). Survival was better in patients with ypT0/is, ypN0 response than in those with residual invasive disease (p < 0.01). 3 year survival was 98.1% for patients with pCR and 92.6% for patients with ypTis, ypN0 response (p = 0.64). CONCLUSIONS: Response rates to trastuzumab based neoadjuvant chemotherapy in Hispanics mimic that of other ethnic groups. This underlines the fact that access to treatment, rather than ethnicity, is the main prognostic factor in this population.

Perfil epidemiológico dos subtipos moleculares de carcinoma ductal da mama em população de pacientes em Salvador, Bahia / Epidemiological profile of molecular subtypes of breast ductal carcinoma in patients population in Salvador, Bahia

Objetivo: Avaliar o perfil dos subtipos moleculares do câncer de mama em uma população de pacientes de duas clínicas privadas de Salvador, Bahia: o Núcleo da Mama e o Núcleo de Oncologia da Bahia. Metodologia: Estudo de corte transversal que incluiu pacientes do sexo feminino com diagnóstico aná- tomo-patológico de carcinoma invasivo sem tipo especial (ductal invasor). Foram excluídas as pacientes com história de câncer prévio, exceto câncer de pele não melanoma; com dados clínicos anteriores ao tratamento sistêmico indisponíveis e sem laudo de imuno-histoquímica. Foi realizada classificação do câncer de mama com base no subtipo molecular em quatro padrões principais: luminal A, luminal B, HER2+ e triplo-negativo. Frequências e proporções foram estabelecidas para cada um dos subtipos moleculares. Outros dados clínicos e laboratoriais também foram colhidos para estabelecer o perfil da população estudada. Resultados: Foram recrutadas 59 pacientes entre dezembro de 2012 e maio de 2014, com idade média de 56,9 anos. O subtipo molecular mais comum na amostra foi o luminal B, com 35 casos (59,3%), seguido do luminal A, (11 casos; 18,6%), triplo-negativo (6 casos, 10,2%) e HER2+ (7 casos; 11,9%). Conclusões: Corroborando outros estudos realizados em população brasileira, o subtipo luminal B é o mais comum encontrado nesta amostra de pacientes de Salvador, Bahia. O achado ajuda a confirmar o padrão atípico do país em relação ao descrito na literatura internacional, com importantes implicações terapêuticas e prognósticas.

Objective: The aim of this study is to evaluate breast cancer molecular subtype distribution in a female population of two private centers in Salvador, Bahia, Brazil: Núcleo da Mama e o Núcleo de Oncologia da Bahia. Methodology: This is a cross-sectional study involving female patients with pathological diagnosis of invasive ductal carcinoma not otherwise specified (NOS). Patients with history of previous cancer except non-melanoma skin câncer; clinical data prior to systemic treatment unavailable and those without immunohistochemical report were excluded from the study. Breast cancer classification was based on four main molecular subtype patterns: luminal A, luminal B, HER2 + and triple negative. Frequencies and proportions were established for each of the molecular subtypes. Other clinical and laboratory data were also collected to determine baseline characteristics of the population studied. Results: We recruited 59 patients between December 2012 and May 2014 with an average age of 56.9 years. The most common molecular subtype of the sample was luminal B subtype, with 35 cases (59.3%), followed by luminal A (11 cases; 18.6%), triple negative (6 cases, 10.2%) and HER2+ (7 cases; 11.9%). Conclusions: Similar to other studies with Brazilian population samples, luminal B subtype is the most common in this sample of patients in Salvador, Bahia. The finding helps confirm the atypical pattern of the country in relation to that described in international literature, with important therapeutic and prognostic implications.

Expresión de Her2/neu en carcinoma gástrico en el área metropolitana de Bucaramanga en el periodo 2006 a 2009 / Her-2/neu expression in gastric cancer in Bucaramanga metropolitan area between 2006 and 2009

Introducción: el cáncer gástrico se ha convertido en un problema de salud pública en el mundo y en Colombia ocupando los primeros lugares en mortalidad. La oncoproteina Her2/neu ha demostrado ser un factor de mal pronóstico independiente, con una expresión variable de 8 a 91% y se asocia a una enfermedad más agresiva y menor respuesta al tratamiento. Objetivo: determinar la frecuencia de expresión de HER-2/neu en carcinoma gástrico y su correlación histopatológica en pacientes del Área Metropolitana de Bucaramanga en el periodo de 2006 a 2009. Materiales y métodos: se realizó un estudio observacional de tipo corte transversal, con una población de 409 casos tomados del Registro Poblacional de Cáncer del Área Metropolitana de Bucaramanga. La información se recolectó de las historias clínicas y los bloques de parafina. Se realizó inmunohistoquímica por el método manual de HERCEPTEST. Los grados 0 y 1 fueron interpretados como negativos, los grados 2 como equívocos y los grados 3 como positivos. A los equívocos se les realizó hibridación inmunofluorecente in situ. Resultados: hubo predominio en hombres con 243 casos, el subtipo histopatológico que prevaleció fue el intestinal con 230 casos, la expresión de HER2/neu fue positiva en 46 casos y no se encontró asociación estadísticamente significativa con el subtipo histopatológico y género. Conclusiones: la expresión de HER2/neu fue positiva en 11,2% de los carcinomas gástricos de los pacientes del Área Metropolitana de Bucaramanga, lo cual es acorde con lo reportado en otros estudios y no hubo asociación estadísticamente significativa con el subtipo histológico y género.

Introduction: gastric cancer has become a public health problem in the world and in Colombia is one of the leading causes of mortality. The oncoprotein Her/2 neu has shown to be an independent bad prognostic factor with a variable expression ranging from 8 - 91% and has been associated with an aggressive disease and a lesser response to treatment. Aim: to determinate the frequency of Her/2 neu and its expression in gastric carcinoma, also its histopathologic correlation in patients from the Bucaramanga Metropolitan Area during 2006 to 2009. Materials and methods: we conducted an observational cross-sectional study with a population of 409 cases from the Population based Cancer Registry from Bucaramanga Metropolitan Area. The information was collected from clinical history and paraffin blocks. The immunochemistry was made with manual HERCEPTEST method. Scores 0 and 1 were interpretated as negative, score 2 as equivocal and score 3 as positive. The samples that were equivocal underwent fluorescence immunohistochemistry in situ. Results: males predominated with 243 cases, the intestinal type was the more prevalent with 230 cases, Her/2 neu expression was positive in 46 cases and there was no significant statistical association with histopathological subtype or gender. Conclusions: expression of Her/2 neu was positive in 11.2% of gastric carcinomas of patients from Bucaramanga Metropolitan Area, this finding is consistent with other reports, and neither there was any statistical significance association with subtype and gender.

Comparison of nuclear grade and immunohistochemical features in situ and invasive components of ductal carcinoma of breast / Comparação do grau nuclear e perfil imunoistoquímico nos componentes in situ e invasivo de carcinoma mamário

PURPOSE:To compare the prognostic and predictive features between in situ and invasive components of ductal breast carcinomas. METHODS:We selected 146 consecutive breast samples with ductal carcinoma in situ (DCIS) associated with adjacent invasive breast carcinoma (IBC). We evaluated nuclear grade and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6 (CK5/6), and epidermal growth factor receptor (EGFR) in both components, in situ and invasive, and the Ki-67 percentage of cells in the invasive part. The DCIS and IBC were classified in molecular surrogate types determined by the immunohistochemical profile as luminal (RE/PR-positive/ HER2-negative), triple-positive (RE/RP/HER2-positive), HER2-enriched (ER/PR-negative/HER2-positive), and triple-negative (RE/RP/HER2-negative). Discrimination between luminal A and luminal B was not performed due to statistical purposes. Correlations between the categories in the two groups were made using the Spearman correlation method. RESULTS:There was a significant correlation between nuclear grade (p<0.0001), expression of RE/RP (p<0.0001), overexpression of HER2 (p<0.0001), expression of EGFR (p<0.0001), and molecular profile (p<0.0001) between components in situ and IBC. CK 5/6 showed different distribution in DCIS and IBC, presenting a significant association with the triple-negative phenotype in IBC, but a negative association among DCIS. CONCLUSIONS: Our results suggest that classical prognostic and predictive features of IBC are already determined in the preinvasive stage of the disease. However the role of CK5/6 in invasive carcinoma may be different from the precursor lesions.

OBJETIVO: Comparar características prognósticas e preditivas entre os componentes in situ e invasivo de carcinomas ductais da mama. MÉTODOS: Selecionamos 146 amostras mamárias consecutivas com carcinoma ductal in situ (CDIS) associado com carcinoma invasivo (CI) adjacente. Avaliamos grau nuclear e a expressão imunoistoquímica de receptor de estrogênio (RE), receptor de progesterona (RP), receptor do fator de crescimento epidérmico humano 2 (HER2), citoqueratina 5/6 (CK5/6) e o receptor do fator de crescimento epidérmico (EGFR) em ambos componentes, in situ e invasor, e a porcentagem de células marcadas pelo Ki-67 no componente invasivo. CDIS e CI foram classificados nos tipos moleculares, determinados pelo perfil imunoistoquímico, como luminal (RE/RP-positivo/HER2-negativo), triplo-positivo (RE/RP/HER2-positivo), HER2-puro (RE/RP-negativo/HER2-positivo) e triplo-negativo (RE/RP/HER2-negativo). A discriminação entre luminal A e Luminal B não foi feita por motivos estatísticos. Correlações entre as categorias dos dois grupos foram feitas pelo método de correlação de Spearman. RESULTADOS: Houve significante associação entre grau nuclear (p<0,0001), expressão de RE/RP) (p<0,0001), superexpressão de HER2 (p<0,0001), expressão de EGFR (p<0,0001) e perfil molecular (p<0,0001) entre os componentes in situ e invasivo. CK5/6 mostrou distribuição distinta em CDIS e CI, apresentando significante associação com o fenótipo triplo-negativo em CI, mas uma associação negativa ente os CDIS. CONCLUSÕES:Nossos resultados sugerem que as características prognósticas e preditivas clássicas dos CI estão já determinadas no estágio pré-invasivo da doença. Entretanto, o papel da CK5/6 no carcinoma invasivo pode ser diferente daquele das lesões precursoras.